The principal goal of this project is to elucidate the pathogenetic role of the clotting system in cell interaction, including tumor rejection. By means of in vivo experiments in guinea pigs, we will investigate the role of fibrinogen in a variety of cell-mediated hypersensitivity reactions, including tuberculin-type delayed skin reactions, systemic delayed hypersensitivity, the macrophage disappearance reaction, and macrophage-tumor cell interactions. Activation of the clotting and kinin system in intravascular cell-mediated reactions will be determined. In vitro studies will attempt to elucidate the function of the newly described macrophage cell-surface fibrinogen. The nature and specificity of the macrophage fibrinogen/fibrin receptor will be determined, as well as the potentiality of macrophages to synthesize fibrinogen. The possible role of surface fibrinogen in other cells, including virus (SV40) transformed and untransformed 3T3 cells, will be examined. The role of the surface fibrinogen and other clotting components in macrophage adherence phenomena and migration will be studied by means of several new assays for cell adherence and by macrophage migration from capillary tubes. Emphasis will be placed on detecting the possible relationships between lymphokines (especially migration inhibitory factor) and fibrinolytic components of the clotting system. BIBLIOGRAPHIC REFERENCES: Golvin, R.B., Gardner, P.I., Roblin, R.O., Verderber, E.L. and Mosesson, M.W.: Cell surface fibrinogen/fibrin (Fib) receptors on cultured human fibroblasts: relationship to cold insoluble globulin and viral transformation. (Abst.) Fed. Proc. 36-316, 1977. Roblin, R.O., Hammond, M.E., Bensky, N.D., Dvorak, A.M., Dvorak, H.F. and Black, P.H.: Generation of macrophage migration inhibitory activity by plasminogen activators. Proc. Nat. Acad. Sci., in press, April, 1977.